Kodiak Sciences Inc · NASDAQ:KOD
Kodiak Sciences — AAO – Retina Subspecialty Day 2020
30 slides from Kodiak Sciences's conference presentation, Nov 11, 2020
Slide 1: One Year and Beyond: Long-Term Multiple-Dose Study of KSI-301 in wAMD, DME, and RVO
One Year and Beyond: Long-Term Multiple- Dose Study of KSI-301, an Anti-VEGF Antibody Biopolymer Conjugate with Extended Durability, in wAMD, DME, and RVO Arshad M. Khanani, MD, MA Director of Clinical Research Sierra Eye Associates Reno, NV AAO – Retina Subspecialty Day 2020 1
Slide 2: Disclosures
Disclosures ▪ Financial: ▪ Grant support: Adverum, Allergan, Chengdu Kanghong, Genentech, Graybug, Gyroscope, Gemini Therapeutics, Kodiak Sciences, Novartis, Iveric Bio, Opthea, Oxurion, Recens Medical, Roche, Regenxbio ▪ Consultant: Adverum, Allergan, Bausch and Lomb, Chengdu Kanghong, DORC, Eyepoi
Slide 3: Current anti-VEGF agents require high-frequency treatment to be most efficacious in DME
Current anti-VEGF agents require high-frequency treatment to be most efficacious in DME Mean number of injections required in Year 1 9.2 9.7 9.4 Maintenance 3.7 3.2 3.4 doses Monthly loading doses 6.0 6.0 6.0 Aflibercept Bevacizumab Ranibizumab DRCR.net Protocol T1 1. Wells JA. Aflibercept, bevacizu
Slide 4: How many KSI-301 injections are needed to achieve these results in DME?
How many KSI-301 injections are needed to achieve these results in DME? 80 +6.6 ETDRS letters ⁓20/32+2 75 BCVA 70 65 0 4 8 12 16 20 24 28 32 36 40 44 500 Weeks 450 OCT CST microns 400 350 300 -132 250 N=18 Patients reaching Week 44 visit by data cutoff Interim data. Includes only randomized patients
Slide 5: Only loading doses and 0.6 mean individualized doses of KSI-301 demonstrate strong efficacy
Only 3 loading doses and 0.6 mean individualized doses of KSI-301 demonstrate strong efficacy 80 +6.6 ETDRS letters ⁓20/32+2 Injections over 75 3.6 44 weeks BCVA Individualized 70 0.6 doses 65 0 4 8 12 16 20 24 28 32 36 40 44 Monthly loading 500 Weeks 3.0 doses 450 KSI-301 OCT CST microns 400 350 67
Slide 6: With only 3 loading doses, what is the durability profile of KSI-301 in DME?
With only 3 loading doses, what is the durability profile of KSI-301 in DME? 6
Slide 7: KSI-301 in DME: loading doses can provide sustained disease control of 3 to 6+ months
KSI-301 in DME: 3 loading doses can provide sustained disease control of 3 to 6+ months Loading Durability Assessment Phase Overall Time on Study (weeks) 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 Percentage 1 First Retreatment KSI-301 3 n=33 5 2.5 mg (n=9) 7 At 2 months 3% 9 1 3 months or l
Slide 8: How can KSI-301 achieve strong efficacy and remarkable durability?
How can KSI-301 achieve strong efficacy and remarkable durability? 8
Slide 9: Antibody Biopolymer Conjugates (ABC)
Antibody Biopolymer Conjugates (ABC) Biologics precision-engineered for increased durability and efficacy SAME WHERE IT MATTERS Single Site-Specific • Clinically proven targets + Stable (Covalent) = • Antibody-based biologic • Intravitreal: safest method of administration Linkage • Optically clear,
Slide 10: KSI-301: Next-Generation anti-VEGF
KSI-301: Next-Generation anti-VEGF ABC Platform and higher dose for longer treatment duration Ranibizumab Bevacizumab Aflibercept KSI-301 Recombinant fusion Antibody Biopolymer Molecule type Antibody fragment Antibody protein Conjugate (ABC) Molecular structure Molecular weight 48 kDa 149 kDa 115 kD
Slide 11: A new set of integrated properties
A new set of integrated properties More than the sum of its parts Remarkable Intraocular Excellent Retinal Deeper Inhibitory Half-life1 Bioavailability2 Potency3 KSI-301 half-life (rabbit) Primary human retinal cell-based assay 10,000.000 • 10.5 days retina Retina Anti-VEGF inhibition of HRMVEC prol
Slide 12: Are there any additional features of KSI-301 in DME seen on imaging?
Are there any additional features of KSI-301 in DME seen on imaging? 12
Slide 13: Sustained DME control for 12 months with only 3 loading doses can be achieved with KSI-301
Sustained DME control for 12 Months with only 3 loading doses can be achieved with KSI-301 3 Loading doses Day 1 Day 1 (Pre-Treatment) Week 4 Week 8 Week 12 1 month after 3 OCT Images loading doses From Phase 1b Study +3 letters 3 total injections in Year 1 6 months after 3 Week 32 loading doses +7
Slide 14: Sustained disease control with only loading doses also seen in proliferative diabetic retinopathy
The sustained disease control of only 3 loading doses of KSI-301 is also seen in proliferative diabetic retinopathy DAY 1 WEEK 12 WEEK 72 Proliferative DR (DRSS 65) Non-Proliferative DR (DRSS 53) Non-Proliferative DR (DRSS 53) KSI-301 Two 5 mg additional 3 loading doses doses Regression from PDR to
Slide 15: Regression from PDR to NPDR with signs of peripheral vascular reperfusion
In addition to the regression from PDR to NPDR, this patient exhibits signs of peripheral vascular reperfusion DAY 1 WEEK 72 Proliferative DR (DRSS 65) Non-Proliferative DR (DRSS 53) PDR KSI-301 5 mg Peripheral ischemia Sustained signs of disease modification for 18 months with only 2 additional dos
Slide 16: How do the Phase 1b Study data inform the design of KSI-301 DME pivotal studies?
How do the Phase 1b Study data inform the design of KSI-301 DME pivotal studies? 16
Slide 17: KSI-301 Phase 3 DME GLEAM and GLIMMER Studies
KSI-301 Phase 3 DME GLEAM and GLIMMER Studies Dosing with KSI-301 as infrequently as every 24 weeks* DME – Phase 1b Now recruiting: GLEAM-GLIMMER pivotal studies Percentage evaluate individualized dosing of every 8, 12, 16, 20 or First Retreatment (n= 33) 24 weeks, after only 3 loading doses At 2 mo
Slide 18: Projecting Phase 1b data into GLEAM and GLIMMER
Projecting Phase 1b data into GLEAM and GLIMMER Potential for dramatic treatment burden reduction in DME Mean number of injections required 9.2 Maintenance 3.2 Treatment burden doses could be reduced 5.0 Individualized 4.8 by almost half doses 0.8 over 2 years Mandatory doses 1.0 3.1 (14.2 vs 7.9 1.
Slide 19: Are there supportive data for KSI-301 in other retinal diseases?
Are there supportive data for KSI-301’s efficacy and durability in other retinal diseases? 19
Slide 20: Strong efficacy and remarkable durability of KSI-301 consistently seen in wAMD
The strong efficacy and remarkable durability of KSI-301 is consistently seen in wAMD ETDRS letters +5.8 BCVA 20/40 1.32 mean injections 44% of which were mandated Q6M doses Weeks OCT CST microns -73 Interim data. Includes only randomized patients that reached Week 44 visit by the data cutoff date o
Slide 21: KSI-301 Phase 2b/3 wAMD DAZZLE Study
KSI-301 Phase 2b/3 wAMD DAZZLE Study Dosing with KSI-301 as infrequently as every 20 weeks* Wet AMD – Phase 1b DAZZLE pivotal study evaluates individualized Percentage First Retreatment (n=49) dosing of every 12, 16 or 20 weeks At or before 2 months 8% 3 months or longer 92% 4 months or longer 82% 5
Slide 22: Efficacy of KSI-301 in RVO
Efficacy of KSI-301 in RVO change from baseline to week 44 in mean BCVA & OCT +22.4 ETDRS letters ⁓20/32 BCVA 1.33 mean injections Only 36% of patients received >1 retreatment Weeks OCT CST microns -370 Interim data. Includes only randomized patients that reached Week 44 visit by the data cutoff dat
Slide 23: KSI-301 Phase 3 RVO BEACON Study
KSI-301 Phase 3 RVO BEACON Study Two loading doses with KSI-301 + every 8 weeks RVO – Phase 1b BEACON pivotal study evaluates two loading doses and Percentage every 8-week dosing, followed by individualized dosing First Retreatment (n= 34) At 1 month 6% 2 months or longer 94% 3 months or longer 66%
Slide 24: Safety
KSI-301 Phase 1b Safety 24
Slide 25: Safety of KSI-301: multiple-dose exposure is well-tolerated
Safety of KSI-301: multiple-dose exposure is well-tolerated 130 622 130 + 121 92 Subjects dosed Total doses Patient-years Completed the Phase 1b subjects at Week 12 or later that Across the Phase 1a/1b program loading phase in have received all three loading doses plus Phase 1b at least one addition
Slide 26: Conclusion
Conclusion ▪ Antibody Biopolymer Conjugates (ABCs) are a new design platform for long durability intravitreal medicines – KSI-301, KSI-501 (anti-VEGF/IL-6 dual inhibitor) and KSI-601 (novel “triplet” inhibitor for dry AMD) ▪ Phase 1b exploratory study informs pivotal study designs – Excellent Safety
Slide 27: Acknowledgements
Acknowledgements Principal Investigators Kodiak Sciences ▪ Mark Barakat, MD ▪ Pablo Velazquez-Martin, MD ▪ Brian Berger, MD ▪ Amy Duguay, BS ▪ David Boyer, MD ▪ Pam Henderson, RN ▪ David Brown, MD ▪ Sinette Heys ▪ Pravin Dugel, MD ▪ Daniel Janer, MD ▪ David Eichenbaum, MD ▪ Hong Liang, PhD ▪ Arshad
Slide 28: Appendix
KSI-301 Phase 1b Appendix 28
Slide 29: KSI-301 Phase 1b Study Design
KSI-301 Phase 1b Study Design Randomized, open label study to evaluate multidose safety, efficacy & durability wAMD (n=51) DME (n=35) RVO (n=35) Randomized 1:3 KSI-301 2.5 mg (50 mL) KSI-301 5 mg (100 mL) Loading Phase Durability Assessment Phase Extension Study Weeks 0 4 8 12 to 72 (months 3 to 18)
Slide 30: KSI-301 Phase 1b Retreatment Criteria
KSI-301 Phase 1b Retreatment Criteria ▪ wAMD – Increase in CST ≥75 µm with a decrease in BCVA of ≥ 5 letters compared to Week 12, OR – Decrease in BCVA of > 5 letters compared to Day 1, due to worsening wAMD activity, OR – Decrease in BCVA of ≥ 10 letters compared to the best prior BCVA, due to wors